YAP: a novel target for Alzheimer's disease

Xu, Xingxing; Wang, Ying; Huang, Zhihui

doi:10.18632/aging.204045

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…Several core components of the Hippo signaling pathway, especially YAP, have been reported to play a crucial role in neurodegenerative disease, being involved in the regulation of neural cellular apoptosis [ 37 ], and YAP has been recently implicated as a hub molecule in AD pathology [ 38 , 61 ]. Likewise, this study showed evidence of the targeting potential of this pathway in AD prevention and treatment.…”

Section: Discussionmentioning

confidence: 99%

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Zhou¹,

Lei²,

Yang³

et al. 2023

IJMS

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Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of Artemisia annua (A. annua) extract on AD. Nine-month-old female 3xTg AD mice were treated with A. annua extract for three months via oral administration. Animals assigned to WT and model groups were administrated with an equal volume of water for the same period. Treated AD mice significantly improved the cognitive deficits and exhibited reduced Aβ accumulation, hyper-phosphorylation of tau, inflammatory factor release and apoptosis when compared with untreated AD mice. Moreover, A. annua extract promoted the survival and proliferation of neural progenitor cells (NPS) and increased the expression of synaptic proteins. Further assessment of the implicated mechanisms revealed that A. annua extract regulates the YAP signaling pathway in 3xTg AD mice. Further studies comprised the incubation of PC12 cells with Aβ1–42 at a concentration of 8 μM with or without different concentrations of A. annua extract for 24 h. Obtained ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis and assessment of the signaling pathways involved was performed using western blot and immunofluorescence staining. The obtained results showed that A. annua extract significantly reversed the Aβ1–42-induced increase in ROS levels, caspase-3 activity and neuronal cell apoptosis in vitro. Moreover, either inhibition of the YAP signaling pathway, using a specific inhibitor or CRISPR cas9 knockout of YAP gene, reduced the neuroprotective effect of the A. annua extract. These findings suggest that A. annua extract may be a new multi-target anti-AD drug with potential use in the prevention and treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Zhou¹,

Lei²,

Yang³

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…3 It has been well documented that YAP plays a critical role in AD. [4][5][6] For example, YAP inhibits early neuronal death and reduces late extracellular Aβ deposition. Moreover, YAP can rescue astrocyte senescence by regulating CDK6 signaling and improving cognitive function in AD model mice.…”

Section: Introductionmentioning

confidence: 99%

“…Vestigial‐like family member 4 (VGLL4) 2 is a new component of the Hippo‐YAP pathway 3 . It has been well documented that YAP plays a critical role in AD 4–6 . For example, YAP inhibits early neuronal death and reduces late extracellular Aβ deposition.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia‐sensing VGLL4 promotes LDHA‐driven lactate production to ameliorate neuronal dysfunction in a cellular model relevant to Alzheimer's disease

Tian,

Li,

et al. 2023

The FASEB Journal

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Alzheimer's disease (AD) is a neurodegenerative disease where abnormal amyloidogenic processing of amyloid‐β precursor protein (APP) occurs and has been linked to neuronal dysfunction. Hypometabolism of glucose in the brain can lead to synaptic loss and neuronal death, which in turn exacerbates energy deficiency and amyloid‐β peptide (Aβ) accumulation. Lactate produced by anaerobic glycolysis serves as an energy substrate supporting neuronal function and facilitating neuronal repair. Vestigial‐like family member 4 (VGLL4) has been recognized as a key regulator of the hypoxia‐sensing pathway. However, the role of VGLL4 in AD remains unexplored. Here, we reported that the expression of VGLL4 protein was significantly decreased in the brain tissue of AD model mice and AD model cells. We further found that overexpression of VGLL4 reduced APP amyloidogenic processing and ameliorated neuronal synaptic damage. Notably, we identified a compromised hypoxia‐sensitive capability of LDHA regulated by VGLL4 in the context of AD. Upregulation of VGLL4 increased the response of LDHA to hypoxia and enhanced the expression levels of LDHA and lactate by inhibiting the ubiquitination and degradation of LDHA. Furthermore, the inhibition of lactate production by using sodium oxamate, an inhibitor of LDHA, suppressed the neuroprotective function of VGLL4 by increasing APP amyloidogenic processing. Taken together, our findings demonstrate that VGLL4 exerts a neuroprotective effect by upregulating LDHA expression and consequently promoting lactate production. Thus, this study suggests that VGLL4 may be a novel player involved in molecular mechanisms relevant for ameliorating neurodegeneration.

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An update on the role of Hippo signaling pathway in ischemia-associated central nervous system diseases

Xuan¹,

Huang²,

Liu³

et al. 2023

Biomedicine & Pharmacotherapy

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YAP: a novel target for Alzheimer's disease

Cited by 6 publications

References 8 publications

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Hypoxia‐sensing VGLL4 promotes LDHA‐driven lactate production to ameliorate neuronal dysfunction in a cellular model relevant to Alzheimer's disease

An update on the role of Hippo signaling pathway in ischemia-associated central nervous system diseases

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